Microscopic analysis of tissue mounted on glass slides is commonly used to study cancer, non-neoplastic entities such as heart disease and diabetes, and normal cell function. Researchers utilize micro and macro tissue dissection techniques in order to recover specific areas of these tissue sections from the slides for subsequent molecular analysis including real time PCR, microarrays, sequencing, and mass spectrometry. When the area to be dissected is relatively large (a few mm), manual macrodissection is adequate. If single cell resolution is required, Laser Microdissection (LMD) is often employed. Both of these methods have their short comings, particularly when an intermediate level of resolution is needed (100m to 1 mm). The Phase II project continues the goal to develop the MESO system, which is an affordable, easy to use, tissue milling and fragment recovery technology for slide mounted tissue sections. AvanSci Bio has met the Specific Aims of the Phase I grant by developing the manufacturing prototype and successfully completing the planned performance evaluation experiments. However, challenging improvements in accuracy, resolution, and sample preparation methods are necessary to expand the usability of the MESO system. In addition, significantly more testing and validation are necessary to ensure the system performs reliably and up to expectations and to encourage adoption. The two Specific Aims of this Phase II include: 1) optimization of sample prep and milling conditions, beta site testing including performance evaluation and validation, and novel application development; and 2) design refinement primarily to the stage precision and blade pressure control, and improved hardness of xScisor blade and more refined fluid control. This new technology and product is expected to further research and clinical diagnostics by greatly reducing the cost and therefore broadening availability of high performance microdissection. We have demonstrated feasibility for Phase II development and commercialization. Our Phase III goal will be to ultimately manufacture and distribute the MESO System, including instrumentation, software, and consumables to clinicians and researchers doing slide mounted tissue dissection.